Cardiac troponin I autoantibody induces myocardial dysfunction by PTEN signaling activationResearch in context
Yu Wu,
Yang-hua Qin,
Yang Liu,
Li Zhu,
Xian-xian Zhao,
Yao-yang Liu,
Shi-wen Luo,
Gu-sheng Tang,
Qian Shen
Affiliations
Yu Wu
Outpatient Department, Changcheng Hospital, Nanchang University, Nanchang, Jiangxi 330002, China; Department of Laboratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
Yang-hua Qin
Department of Laboratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
Yang Liu
Department of Cardiothoracic Surgery, Changhai Hospital, Second military Medical University, Shanghai 200433, China
Li Zhu
Department of Laboratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China; Department of Laboratory Medicine, Wuxi First People Hospital, Wuxi, Jiangsu 214002, China
Xian-xian Zhao
Department of Cardiology, Changhai Hospital, Second military Medical University, Shanghai 200433, China
Yao-yang Liu
Department of Rheumatology, Changzheng Hospital, Second military Medical University, Shanghai 200003, China
Shi-wen Luo
Research Center, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
Gu-sheng Tang
Department of Hematology, Changhai Hospital, Second military Medical University, Shanghai 200433, China; Correspondence to: G. Tang, Department of Hematology, Changhai Hospital, Second Military Medical University, No.168, Changhai Road, Shanghai 200433, China.
Qian Shen
Department of Laboratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China; Correspondence to: Q. Shen, Department of Laboratory Medicine, Changhai Hospital, Second Military Medical University, No.168, Changhai Road, Shanghai 200433, China.
Background: The objective of the current study was to study the molecular mechanism(s) underlying cardiac troponin I autoantibody (cTnIAAb) binding to cardiomyocyte and resultant myocardial damage/dysfunction. Methods: cTnIAAb was purified from serum of 10 acute myocardial infarction (AMI) patients with left ventricular remodeling. Recombinant human cTnI was used to generate three mouse-derived monoclonal anti-cTnI antibodies (cTnImAb1, cTnImAb2, and cTnImAb3). The target proteins in cardiac myocyte membrane bound to cTnImAb and effect of cTnIAAb and cTnImAb on apoptosis and myocardial function were determined. Findings: We found that cTnIAAb/cTnImAb1 directly bound to the cardiomyocyte membraneα-Enolase (ENO1) and triggered cell apoptosis via increased expression of ENO1 and Bax, decreased expression of Bcl2, subsequently activating Caspase8, Caspase 3, phosphatase and tensin homolog (PTEN) while inhibiting Akt activity. This cTnIAAb-ENO1-PTEN-Akt signaling axis contributed to increased myocardial apoptosis, myocardial collagen deposition, and impaired systolic dysfunction. Interpretation: Results obtained in this study indicate that cTnIAAb is involved in the process of ventricular remodeling after myocardial injury. Fund: The National Natural Science Foundation of China (Grant#: 81260026). Keywords: Acute myocardial infarction, Cardiac troponin I autoantibody, Phosphatase and tensin homolog, Ventricular remodeling, α-Enolase
